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Early Childhood Wheezing Phenotypes and Determinants in a South African Birth Cohort Study
26 Pages Posted: 28 Jul 2022
More...Abstract
Background: Developmental trajectories of childhood wheezing in low- and middle-income countries (LMICs) have not been well described.
Methods: In a South African birth cohort (DCHS), we derived 6 multi-dimensional indicators of wheezing spells from birth to age 5 years (including duration, temporal sequencing, persistence/recurrence), and applied Partition-Around-Medoids clustering to derive wheezing phenotypes. We compared phenotypes to those in a UK cohort (ALSPAC). We investigated associations of derived phenotypes with early-life exposures, including all-cause lower respiratory tract infection (LRTI) and virus-specific LRTI (respiratory syncytial virus-RSV, rhinovirus-RV, adenovirus-AV). Finally, we investigated the association of wheeze clusters with lung function (oscillometry) at 6 weeks and 5 years.
Findings: Analysis amongst 950 children with complete data identified 4 spell-based wheeze phenotypes: Never (50·5%), Early transient (22·6%), Late-onset (11%) and Recurrent (15·9%). Early-life factors common in LMICs increased the risk of Recurrent wheeze, including LRTI and RSV-LRTI, maternal smoking and intimate partner violence. RSV-LRTI was also associated with Early transient cluster. In contrast AV-LRTI was associated with Late-onset wheezing. Wheezing illness architecture differed in ALSPAC; although some clusters appeared similar, in ALSPAC children in Early transient cluster wheezed longer before remission, and Late-onset wheezing started later. At age 5 years, lung function was significantly diminished in Early transient and Recurrent wheeze, and it declined between ages 6 weeks and 5 years amongst recurrent wheezers.
Interpretation: Effective strategies to reduce maternal psychosocial stressors and smoking, and new preventive interventions for RSV are urgently needed to optimise child health in LMIC setting.
Funding Information: This analysis was funded by the UK-MRC grant number MR/S002359/1. DCHS is also funded by the Bill & Melinda Gates Foundation, USA (grant number OPP1017641, OPP1017579), Wellcome Trust (grant number 204755/z/16/z) and the NIH H3 Africa (grant numbers U54HG009824, U01AI110466). HZ is supported by the SA MRC. DG is supported by the Wellcome Trust.
Declaration of Interests: HJZ reports grants from the Bill & Melinda Gates Foundation, the NIH H3 Africa, the UK MRC and the SA-MRC. DG reports grants from the Wellcome Trust. AC reports personal fees from Stallergenes Greer, personal fees from AstraZeneca, personal fees from GSK, personal fees from Worg Pharmaceuticals, outside the submitted work. All other authors have nothing to declare.
Ethics Approval Statement: The study was approved by the local Research committees. Mothers gave written informed consent at enrolment and were re-consented annually. The study was approved by the Human Research Ethics Committee of the Faculty of Health Sciences, University of Cape Town, South Africa.
Keywords: wheezing phenotypes, birth cohort, lung function, lower respiratory tract infection, RSV
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